What are the causes of hypercalcemia (elevated calcium)?

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From the Guidelines

Elevated calcium, known as hypercalcemia, is a condition that can lead to a range of symptoms and complications, including kidney stones, bone pain, and cardiac arrhythmias, and is most commonly caused by primary hyperparathyroidism, as noted in the 2021 study published in the Journal of the American College of Radiology 1. The symptoms and complications of hypercalcemia can vary in severity, but commonly include:

  • Kidney stones
  • Bone pain
  • Excessive urination
  • Abdominal pain
  • Nausea
  • Vomiting
  • Constipation
  • Fatigue
  • Muscle weakness
  • Cognitive changes like confusion In severe cases, hypercalcemia can cause cardiac arrhythmias, coma, and even death. The most common causes of hypercalcemia are primary hyperparathyroidism and malignancy, with primary hyperparathyroidism being the most common cause, accounting for approximately 80% of cases, as stated in the study published in the Journal of the American College of Radiology 1. Treatment of hypercalcemia depends on the severity and underlying cause, and can range from increased fluid intake to medications like bisphosphonates, calcitonin, or cinacalcet, as suggested in the studies published in the Annals of Internal Medicine 1. In severe cases with calcium >14mg/dL, aggressive IV fluid rehydration with normal saline at 200-300mL/hour is often necessary, followed by loop diuretics once hydration is restored, as a general approach to managing severe hypercalcemia. It is essential to note that hypercalcemia occurs when calcium regulation mechanisms fail, particularly when parathyroid hormone levels are inappropriately elevated or when tumors release substances that increase bone resorption, releasing more calcium into the bloodstream, as explained in the study published in the Journal of the American College of Radiology 1. The management of hypercalcemia should prioritize the correction of the underlying cause, whether it be primary hyperparathyroidism or malignancy, and should aim to restore normal calcium levels to prevent long-term complications, as emphasized in the studies published in the Annals of Internal Medicine 1.

From the FDA Drug Label

Excessive release of calcium into the blood as bone is resorbed results in polyuria and gastrointestinal disturbances, with progressive dehydration and decreasing glomerular filtration rate This, in turn, results in increased renal resorption of calcium, setting up a cycle of worsening systemic hypercalcemia. Elevated calcium causes:

  • Polyuria
  • Gastrointestinal disturbances
  • Progressive dehydration
  • Decreasing glomerular filtration rate 2

From the Research

Causes and Effects of Elevated Calcium

  • Elevated calcium, also known as hypercalcemia, can be caused by various factors, including primary hyperparathyroidism (PHPT) and malignancy, which account for approximately 90% of all cases 3, 4, 5.
  • Other causes of hypercalcemia include granulomatous disease, endocrinopathies, immobilization, genetic disorders, and certain medications such as thiazide diuretics and supplements like calcium, vitamin D, or vitamin A 3.
  • Hypercalcemia can lead to various symptoms, including nausea, vomiting, dehydration, confusion, somnolence, and coma, especially in severe cases 3, 4, 5.
  • Mild hypercalcemia is usually asymptomatic, but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people 3.

Diagnosis and Treatment

  • The diagnosis of hypercalcemia involves measuring serum calcium levels and parathyroid hormone (PTH) concentrations 3, 4, 5.
  • Treatment of hypercalcemia depends on the underlying cause and severity of the condition, and may include hydration, intravenous bisphosphonates, glucocorticoids, and parathyroidectomy in some cases 3, 4, 5, 6.
  • Medical management of primary hyperparathyroidism (PHPT) may include optimizing calcium and vitamin D intake, antiresorptive therapy, and cinacalcet, a calcimimetic agent 6.
  • Vitamin D supplementation can increase the risk of hypercalcemia and hypercalciuria, but does not appear to increase the risk of kidney stones 7.

Clinical Manifestations

  • Clinical manifestations of hypercalcemia are related to calcium levels, with higher values leading to more pronounced symptoms 4.
  • Severe hypercalcemia can affect various systems, including neurological, muscular, gastrointestinal, renal, and cardiovascular systems 4.
  • Critically ill patients with hypercalcemia should receive treatment as soon as diagnosis is made 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hypercalcemia: A Review.

JAMA, 2022

Research

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Medical science monitor : international medical journal of experimental and clinical research, 2022

Research

Hypercalcemia: an evidence-based approach to clinical cases.

Iranian journal of kidney diseases, 2009

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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